RBM15, an m6A enzyme, suppresses NLRP3 inflammasome activation in rheumatoid arthritis through macrophage metabolism
Authors' conclusion
The m6A enzyme RBM15 mitigates RA damage by reducing macrophage glycolysis and inhibiting NLRP3 inflammasome activation.
Study context
- Population
- Synovial biopsy samples from rheumatoid arthritis (RA) patients; LPS-stimulated macrophages; Collagen-induced arthritis (CIA) mice
- Comparison
- RBM15 overexpression (RBM15-adenovirus (RBM15-Ad)) vs control adenovirus (Con-Ad) in CIA mice; RBM15 expression in RA vs healthy controls (HC)
Methodological detailsin vivo and in vitro, GSE77298 analysis, collagen-induced arthritis mouse model
- In vivo and in vitro
- GSE77298 analysis
- Collagen-induced arthritis mouse model
Main finding
As reported in the abstract
- RBM15 expression significantly reduced in RA vs HC (real-time PCR)
- RBM15 overexpression reversed LPS-induced rise in M1 markers (CXCL9, CXCL10) and fall in M2 markers (ARG1, MRC1)
- RBM15 overexpression reversed LPS-induced increase in macrophage glycolysis
- RBM15 knockdown significantly promoted NLRP3 inflammasome activation, reversed by glycolysis inhibitor 2-DG
- RBM15 overexpression reduced RA symptoms, pathological damage and inflammatory responses in CIA mice
- NLRP3 inflammasome activation suppressed in RBM15-Ad
Original publication
RBM15, an m6A enzyme, suppresses NLRP3 inflammasome activation in rheumatoid arthritis through macrophage metabolism. Clin Exp Rheumatol. Published 26 August 2024. doi:10.
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